Treatment of Obesity and/or Type II Diabetes by Stimulation of the Pituitary Gland

ABSTRACT

Methods of treating obesity and/or type II diabetes include applying at least one stimulus to the pituitary gland of a patient with an implanted stimulator in accordance with one or more stimulation parameters. The at least one stimulus is configured to treat obesity and/or type II diabetes. Systems for treating obesity and/or type II diabetes include a stimulator configured to apply at least one stimulus to the pituitary gland of a patient in accordance with one or more stimulation parameters. The at least one stimulus is configured to treat obesity and/or type II diabetes.

RELATED APPLICATIONS

The present application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Patent Application No. 60/923,369 by Kristen N. Jaax et al.,filed on Apr. 13, 2007, and entitled “Treatment of Obesity and/or TypeII Diabetes by Stimulation of the Pituitary Gland,” the contents ofwhich are hereby incorporated by reference in their entirety.

BACKGROUND

Obesity is one of the most prevalent public heath problems in the UnitedStates and affects millions of Americans. An especially severe type ofobesity, called morbid obesity, is characterized by a body mass indexgreater than or equal to 40 or a body weight that is 100 or more poundsover normal weight.

Recent studies have shown that over 300,000 deaths are caused by obesityin the United States each year. In addition, millions suffer brokenbones, social isolation, arthritis, sleep apnea, asphyxiation, heartattacks, diabetes, and other medical conditions that are caused orexacerbated by obesity.

Patients suffering from obesity have very limited treatment options. Forexample, drugs such as sibutramine, diethylpropion, mazindol,phentermine, phenylpropanolamine, and orlistat are often used to treatobesity. However, these drugs are effective only for short-term use andhave many adverse side-effects.

Another treatment option for obesity is surgery. For example, aprocedure known as “stomach stapling” reduces the effective size of thestomach and the length of the nutrient-absorbing small intestine totreat obesity. However, surgery is highly invasive and is oftenassociated with both acute and chronic complications including, but notlimited to, infection, digestive problems, and deficiency in essentialnutrients.

Obesity is intricately related to diabetes, in particular type IIdiabetes. Type II diabetes is characterized by body tissue resistance toinsulin activity. Many studies suggest that obesity increase a person'schances of developing type II diabetes.

Likewise, type II diabetes increases a person's propensity to becomeobese. As cells within the body become less responsive to the actions ofinsulin, the pancreas is forced to continuously produce more insulin todrive glucose into cells. The excess insulin that is produced as aresult of insulin resistance increases the storage of body fat andthereby increases a person's propensity to become obese.

Patients suffering from type II diabetes also have limited treatmentoptions. Type II diabetes is typically controlled with diet, weightloss, exercise, and oral medications. More than half of all people withtype II diabetes require insulin to control their blood sugar levels atsome point in the course of their illness. However, these treatmentoptions are made difficult when type II diabetes is accompanied byobesity.

SUMMARY

Methods of treating obesity and/or type II diabetes include applying atleast one stimulus to the pituitary gland of a patient with an implantedstimulator in accordance with one or more stimulation parameters. The atleast one stimulus is configured to treat obesity and/or type IIdiabetes.

Systems for treating obesity and/or type II diabetes include astimulator configured to apply at least one stimulus to the pituitarygland of a patient in accordance with one or more stimulationparameters. The at least one stimulus is configured to treat obesityand/or type II diabetes.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate various embodiments of theprinciples described herein and are a part of the specification. Theillustrated embodiments are merely examples and do not limit the scopeof the disclosure.

FIG. 1A depicts the lateral surface of the brain.

FIG. 1B depicts, in perspective view, the thalamus and variousstructures of the brain that make up the limbic system.

FIG. 2 illustrates an exemplary stimulator that may be used to apply astimulus to a stimulation site within a patient to treat obesity and/ortype II diabetes according to principles described herein.

FIG. 3 illustrates an exemplary microstimulator according to principlesdescribed herein.

FIG. 4A shows an example of a microstimulator with one or more leadscoupled thereto according to principles described herein.

FIG. 4B shows an example of a microstimulator with a plurality ofelectrodes disposed on an outer surface thereof according to principlesdescribed herein.

FIG. 4C shows the exemplary microstimulator of FIG. 4B coupled to a leadhaving a number of electrodes disposed thereon according to principlesdescribed herein.

FIG. 5 depicts a number of stimulators configured to communicate witheach other and/or with one or more external devices according toprinciples described herein.

FIG. 6 is a flow chart illustrating an exemplary method of treatingobesity and/or type II diabetes according to principles describedherein.

FIG. 7 illustrates a stimulator that has been implanted beneath thescalp of a patient to stimulate a stimulation site within the brainaccording to principles described herein.

FIG. 8 is cross-sectional view of a stimulator implanted within a holecreated in the skull of a patient according to principles describedherein.

Throughout the drawings, identical reference numbers designate similar,but not necessarily identical, elements.

DETAILED DESCRIPTION

Methods and systems for treating obesity and/or type II diabetes aredescribed herein. An implanted stimulator is configured to apply atleast one stimulus to a stimulation site within a patient in accordancewith one or more stimulation parameters. The stimulus is configured totreat obesity and/or type II diabetes and may include electricalstimulation, drug stimulation, gene infusion, chemical stimulation,thermal stimulation, electromagnetic stimulation, mechanicalstimulation, and/or any other suitable stimulation. As used herein, andin the appended claims, “treating” obesity and/or type II diabetesrefers to any amelioration of one or more causes and/or one or moresymptoms of obesity and/or type II diabetes. For example, treatingobesity and/or type II diabetes as described herein may include, withoutbeing limited to, preventing weight gain, regulating gastrointestinalactivity, creating a sensation of fullness such that the patient eatsless, and/or reducing a sensation of hunger within the patient.

In the following description, for purposes of explanation, numerousspecific details are set forth in order to provide a thoroughunderstanding of the present systems and methods. It will be apparent,however, to one skilled in the art that the present systems and methodsmay be practiced without these specific details. Reference in thespecification to “one embodiment” or “an embodiment” means that aparticular feature, structure, or characteristic described in connectionwith the embodiment is included in at least one embodiment. Theappearance of the phrase “in one embodiment” in various places in thespecification are not necessarily all referring to the same embodiment.

Before discussing the present methods and systems for treating obesityand/or type II diabetes, a brief overview of the brain will be given.FIG. 1A depicts the lateral surface of the brain. As shown in FIG. 1A,the primary motor cortex 100 is located on the lateral surface of thebrain. Activity within the primary motor cortex 100 influences motormovements. Also shown in FIG. 1A are the somatosensory cortex 101,premotor cortex 102, and supplementary motor cortex 103. Thesestructures are also involved in controlling motor movements.

FIG. 1B depicts, in perspective view, the thalamus 104 and variousstructures of the brain that make up the limbic system. The thalamus 104helps process information from the senses and relays such information toother parts of the brain. Located beneath the thalamus is thehypothalamus (not shown). The hypothalamus regulates many bodyfunctions, including appetite and body temperature.

The limbic system shown in FIG. 1B includes, but is not limited to,several subcortical structures located around the thalamus 104.Exemplary structures of the limbic system include the cingulate gyrus105, corpus collosum 106, stria terminalis 107, caudate nucleus 108,basal ganglia 109, hippocampus 110, enterorhinal cortex 111, amygdala112, mammillary body 113, medial septal nucleus 114, prefrontal cortex115, and formix 116. These structures are involved with emotion,learning, and memory.

FIG. 1B also shows the pituitary gland 117. The pituitary gland 117 is asmall gland located at the base of the brain that secretes severaldifferent hormones involved in key metabolic processes throughout thebody. The pituitary gland 117 also controls a number of endocrinesystems in the body. Imbalances in the pituitary gland 117 can increasethe amount of cortisol that is produced by the adrenal glands. It hasbeen discovered that this overproduction of cortisol can lead toovereating and/or increased fat production in the body. Hence, amalfunction of the pituitary gland 117 may lead to obesity and/or typeII diabetes.

It is believed that applying a stimulus to one or more stimulation siteswithin the brain may be useful in treating obesity and/or type IIdiabetes. For example, it is believed that applying a stimulus to thepituitary gland may be useful in treating obesity and/or type IIdiabetes. As mentioned, “treating” obesity and/or type II diabetesrefers to any amelioration of one or more causes and/or symptoms ofobesity and/or type II diabetes. By treating obesity and/or type IIdiabetes, the methods and systems described herein may also be used totreat other diseases or conditions that are sequelae of obesity and/ortype II diabetes such as, but not limited to, obstructive sleep apnea(OSA), hyperlipidemia, infertility, hypertension, metabolic syndrome,osteoarthritis, gastroesophageal reflux disease (GERD), coronary arterydisease, cholelithiasis, hypertriglyceridemia, heart failure, and gout.

Consequently, a stimulator may be implanted within a patient to delivera stimulus to one or more stimulation sites within the patient in orderto treat obesity and/or type II diabetes. The stimulus may include anelectrical stimulation current, one or more drugs or other chemicalstimulation, thermal stimulation, electromagnetic stimulation,mechanical stimulation, and/or any other suitable stimulation.

The one or more stimulation sites referred to herein, and in theappended claims, may include, but are not limited to, any one or more ofthe locations within the brain as described above. For example, thestimulation site may include, but is not limited to, the pituitarygland.

As used herein, and in the appended claims, the term “stimulator” willbe used broadly to refer to any device that delivers a stimulus, such asan electrical stimulation current, one or more drugs or other chemicalstimulation, thermal stimulation, electromagnetic stimulation,mechanical stimulation, and/or any other suitable stimulation at astimulation site to treat obesity and/or type II diabetes. Thus, theterm “stimulator” includes, but is not limited to, a microstimulator,implantable pulse generator (IPG), spinal cord stimulator (SCS), systemcontrol unit, deep brain stimulator, drug pump, or similar device.

To facilitate an understanding of the methods of treating obesity and/ortype II diabetes with an implanted stimulator, a more detaileddescription of a stimulator and its operation will now be given withreference to the figures. FIG. 2 illustrates an exemplary stimulator 120that may be used to apply a stimulus to a stimulation site within apatient, e.g., an electrical stimulation of the stimulation site, aninfusion of one or more drugs at the stimulation site, or both. Theelectrical stimulation function of the stimulator 120 will be describedfirst, followed by an explanation of the possible drug delivery functionof the stimulator 120. It will be understood, however, that thestimulator 120 may be configured to provide only electrical stimulation,only drug stimulation, both types of stimulation, or any other type ofstimulation as best suits a particular patient.

The exemplary stimulator 120 shown in FIG. 2 is configured to provideelectrical stimulation to one or more stimulation sites within a patientand may include at least one lead 121 coupled thereto. In some examples,the at least one lead 121 includes a number of electrodes 122 throughwhich electrical stimulation current may be applied to a stimulationsite. It will be recognized that the at least one lead 121 may includeany number of electrodes 122 arranged in any configuration as bestserves a particular application. In some alternative examples, as willbe described in more detail below, the stimulator 120 may be leadless.

As illustrated in FIG. 2, the stimulator 120 includes a number ofcomponents. For example, the stimulator 120 may include a power source123, coil 124, electrical circuitry 125, a programmable memory unit 126,and/or a pump 127. It will be recognized that the stimulator 120 mayinclude additional and/or alternative components as best serves aparticular application.

The power source 123 is configured to output voltage used to supply thevarious components within the stimulator 120 with power and/or togenerate the power used for electrical stimulation. The power source 123may include a primary battery, a rechargeable battery (e.g., alithium-ion battery), a super capacitor, a nuclear battery, a mechanicalresonator, an infrared collector (receiving, e.g., infrared energythrough the skin), a thermally-powered energy source (where, e.g.,memory-shaped alloys exposed to a minimal temperature differencegenerate power), a flexural powered energy source (where a flexiblesection subject to flexural forces is part of the stimulator), abioenergy power source (where a chemical reaction provides an energysource), a fuel cell, a bioelectrical cell (where two or more electrodesuse tissue-generated potentials and currents to capture energy andconvert it to useable power), an osmotic pressure pump (where mechanicalenergy is generated due to fluid ingress), or the like.

In some examples, the power source 123 may be recharged using anexternal charging system. One type of rechargeable power supply that maybe used is described in U.S. Pat. No. 6,596,439, which is incorporatedherein by reference in its entirety. Other battery constructiontechniques that may be used to make the power source 123 include thoseshown, e.g., in U.S. Pat. Nos. 6,280,873; 6,458,171; 6,605,383; and6,607,843, all of which are incorporated herein by reference in theirrespective entireties.

The stimulator 120 may also include a coil 124 configured to receiveand/or emit a magnetic field (also referred to as a radio frequency (RF)field) that is used to communicate with, or receive power from, one ormore external devices. Such communication and/or power transfer mayinclude, but is not limited to, transcutaneously receiving data from theexternal device, transmitting data to the external device, and/orreceiving power used to recharge the power source 123.

The stimulator 120 may also include electrical circuitry 125 configuredto generate the electrical stimulation current that is delivered to astimulation site via one or more of the electrodes 122. For example, theelectrical circuitry 125 may include one or more processors, capacitors,integrated circuits, resistors, coils, and/or any other componentconfigured to generate electrical stimulation current.

The exemplary stimulator 120 shown in FIG. 2 may additionally oralternatively be configured to provide drug stimulation to a patient byapplying one or more drugs at a stimulation site within the patient. Tothis end, a pump 127 may also be included within the stimulator 120. Thepump 127 may be configured to store and dispense one or more drugs, forexample, through a catheter 128 that is coupled to the stimulator 120.The catheter 128 may be coupled at a proximal end to the stimulator 120and may include an infusion outlet 129 for infusing dosages of the oneor more drugs at the stimulation site. In some embodiments, thestimulator 120 may include multiple catheters 128 and/or pumps forstoring and infusing dosages of the one or more drugs at the stimulationsite.

The one or more drugs applied by the stimulator 120 may include any drugor other substance configured to treat obesity and/or type II diabetes.For example, the one or more drugs that may be applied to a stimulationsite to treat obesity and/or type II diabetes may have an excitatoryeffect on the stimulation site. Additionally or alternatively, the oneor more drugs may have an inhibitory effect on the stimulation site inorder to treat obesity and/or type II diabetes. Exemplary excitatorydrugs that may be applied to a stimulation site to treat obesity and/ortype II diabetes include, but are not limited to, at least one or moreof the following: an excitatory neurotransmitter (e.g., glutamate,dopamine, norepinephrine, epinephrine, acetylcholine, serotonin); anexcitatory neurotransmitter agonist (e.g., glutamate receptor agonist,L-aspartic acid, N-methyl-D-aspartic acid (NMDA), bethanechol,norepinephrine); an inhibitory neurotransmitter antagonist(s) (e.g.,bicuculline); an agent that increases the level of an excitatoryneurotransmitter (e.g., edrophonium, Mestinon); and/or an agent thatdecreases the level of an inhibitory neurotransmitter (e.g.,bicuculline).

Exemplary inhibitory drugs that may be applied to a stimulation site totreat obesity and/or type II diabetes include, but are not limited to,at least one or more of the following: an inhibitory neurotransmitter(s)(e.g., gamma-aminobutyric acid, a.k.a. GABA, dopamine, glycine); anagonist of an inhibitory neurotransmitter (e.g., a GABA receptor agonistsuch as midazolam or clondine, muscimol); an excitatory neurotransmitterantagonist(s) (e.g. prazosin, metoprolol, atropine, benztropine); anagent that increases the level of an inhibitory neurotransmitter; anagent that decreases the level of an excitatory neurotransmitter (e.g.,acetylcholinesterase, Group II metabotropic glutamate receptor (mGluR)agonists such as DCG-IV); a local anesthetic agent (e.g., lidocaine);and/or an analgesic medication. It will be understood that some of thesedrugs, such as dopamine, may act as excitatory neurotransmitters in somestimulation sites and circumstances, and as inhibitory neurotransmittersin other stimulation sites and circumstances.

Additional or alternative drugs that may be applied to a stimulationsite to treat obesity and/or type II diabetes include, but are notlimited to, at least one or more of the following substances: capsaicin,a neurotoxic substance, neurotrophic factors (e.g., brain derivedneotrophic factors (BDNF) and glial cell line derived neurotrophicfactors (GDNF)), steroids, antibiotics, analgesics, gastrin, one or morepeptides (e.g., neuropeptide Y), cholecystokinin (CCK). Capsaicin andneurotoxic substances can act as excitotoxic agents and may be placed onthe olfactory epithelium to decrease perception of scents. Neurotrophicfactors, steroids, and antibiotics have been shown to increase efficacyof drug infusion, reduce fibrosis, and/or prevent infection. Gastrin,peptides, and cholecystokinin modulate intake of food.

Any of the drugs listed above, alone or in combination, or other drugsor combinations of drugs developed or shown to treat obesity and/or typeII diabetes or their respective symptoms may be applied to thestimulation site to treat obesity and/or type II diabetes. In someembodiments, the one or more drugs are infused chronically into thestimulation site. Additionally or alternatively, the one or more drugsmay be infused acutely into the stimulation site in response to abiological signal or a sensed need for the one or more drugs.

The stimulator 120 may also include a programmable memory unit 126configured to store one or more stimulation parameters. The stimulationparameters may include, but are not limited to, electrical stimulationparameters, drug stimulation parameters, and other types of stimulationparameters. The programmable memory unit 126 allows a patient,clinician, or other user of the stimulator 120 to adjust the stimulationparameters such that the stimulation applied by the stimulator 120 issafe and efficacious for treatment of a particular patient. Theprogrammable memory unit 126 may include any type of memory unit suchas, but not limited to, random access memory (RAM), static RAM (SRAM), ahard drive, or the like.

The electrical stimulation parameters may control various parameters ofthe stimulation current applied to a stimulation site including, but notlimited to, the frequency, pulse width, amplitude, waveform (e.g.,square or sinusoidal), electrode configuration (i.e., anode-cathodeassignment), burst pattern (e.g., continuous or intermittent), dutycycle or burst repeat interval, ramp on time, and ramp off time. Thedrug stimulation parameters may control various parameters including,but not limited to, the amount of drugs infused at the stimulation site,the rate of drug infusion, and the frequency of drug infusion. Forexample, the drug stimulation parameters may cause the drug infusionrate to be intermittent, continuous, or bolus.

Specific stimulation parameters may have different effects on differenttypes, causes, or symptoms of obesity and/or type II diabetes. Thus, insome examples, the stimulation parameters may be adjusted at any timethroughout the treatment course as best serves the particular patientbeing treated. It will be recognized that any of the characteristics ofthe stimulation current, including, but not limited to, the pulse shape,amplitude, pulse width, frequency, burst pattern (e.g., continuous orintermittent), duty cycle or burst repeat interval, ramp on time, andramp off time may be adjusted throughout the course of treatment as bestserves a particular application.

To illustrate, a baseline set of stimulation parameters may initially beset to begin treatment of obesity and/or type II diabetes. Thesebaseline values may be adjusted throughout the course of treatment inresponse to patient feedback or sensed indicators of obesity and/or typeII diabetes. Additionally or alternatively, the patient and/or clinicianmay adjust the stimulation parameters at any time to preventaccommodation, collateral stimulation, and/or ineffectiveness.

An exemplary baseline set of stimulation parameters that may be used toinitially define stimulation current that is used to treat obesityand/or type II diabetes includes, but is not limited to the stimulationparameters shown in Table 1. It will be recognized that the baseline setof stimulation parameters shown in Table 1 may vary depending on theparticular patient being treated and that additional or alternativestimulation parameters may be defined.

TABLE 1 Exemplary Baseline Stimulation Parameters Pulse width 10microseconds (μsec) Frequency 30 Hz Burst pattern Continuous Amplitude0.1 milliamps (mA)

Hence, as shown in Table 1, a continuous stimulation current having apulse width of 10 μsec, a frequency of 30 Hz, and an amplitude of 0.1 mAmay be initially applied to a stimulation site within the patient (e.g.,the pituitary gland) in order to treat obesity and/or type II diabetes.The pulse width, frequency, and amplitude may initially have relativelysmall values so as to avoid muscle spasms, nerve damage, or discomfort.

In some examples, these baseline parameters may be determined in theinitial fitting session and may depend on the electrode placement (e.g.,how proximal they are to the stimulation site), local impedance (whichmay be affected by scar tissue, etc.), and patient variability. Theclinician or other programmer may make subtle, iterative adjustments toany of the stimulation parameters in response to real-time feedback fromthe patient.

After a predetermined length of time (e.g., one or more weeks, months,or years) of treatment or as the need may arise, the patient may beevaluated to determine whether the stimulation parameters need to beadjusted and/or whether the additional stimulation is needed in order totreat obesity and/or type II diabetes. In some examples, if the patientno longer exhibits any symptoms of obesity and/or type II diabetes, thestimulation may be terminated. Alternatively, if it is determined thatthe patient needs further treatment, the stimulation may continue inaccordance with the same set of stimulation parameters or in accordancewith a newly defined set of stimulation parameters. For example, thestimulation parameters may be adjusted from the exemplary baselinestimulation parameters described previously in connection with Table 1to have the exemplary values within the ranges shown in Table 2:

TABLE 2 Exemplary Adjusted Stimulation Parameters Pulse width 5 μsecFrequency 120 Hz Burst pattern Continuous Amplitude 0.2 mA

As shown in Table 2, the pulse width, frequency, and/or amplitude may beadjusted so that the stimulation current more effectively treats obesityand/or type II diabetes. For example, the pulse width, frequency, and/oramplitude may be adjusted to more suitable values. It will be recognizedthat the values shown in Table 2 are merely illustrative and that theymay vary as may serve a particular application. It will also berecognized that any other stimulation parameter (e.g., one or more ofthe drug stimulation parameters) may additionally or alternatively beadjusted in order to more effectively treat obesity and/or type IIdiabetes.

In some examples, the stimulation parameters may be configured toprovide monopolar electrical stimulation. For example, an external caseof the stimulator 120 may be used as an indifferent electrode. In otherembodiments, the stimulation parameters may be configured to providebipolar electrical stimulation (e.g., one of the electrodes 122 may beused as an indifferent electrode). Different stimulation parameters mayhave different effects on neural or other tissue. Therefore, parametersmay be chosen to target specific neural or other tissue populationsand/or exclude others in order to achieve a desired therapeutic effect.Additionally, the stimulation parameters may provide for currentsteering between electrodes 122 such that one or more specificstimulation sites may be targeted.

In some examples, it may be desirable to increase excitement of astimulation site in order to treat obesity and/or type II diabetes. Tofacilitate increased excitement of a stimulation site, the stimulationparameters may be adjusted such that the stimulator 120 applies astimulation current having a relatively low frequency (e.g., less than100 Hz) to the stimulation site.

In some alternative examples, it may be desirable to decrease excitementof a stimulation site in order to treat obesity and/or type II diabetes.To facilitate decreased excitement of a stimulation site, thestimulation parameters may be adjusted such that the stimulator 120applies a stimulation current having a relatively high frequency (e.g.,greater than 100 Hz) to the stimulation site.

The stimulation parameters may also be adjusted such that the electricaland/or drug stimulation is applied to a stimulation site eitherintermittently or continuously. Intermittent stimulation may be moreeffective than continuous stimulation in some instances and vice versa.

It will be recognized that different stimuli may be applied to differentstimulation sites to most effectively treat obesity and/or type IIdiabetes for a particular patient. Moreover, the stimulation parametersmay be adjusted by the patient, a clinician, or other user of thestimulator 120 as best serves the particular patient being treated. Thestimulation parameters may additionally or alternatively beautomatically adjusted by the stimulator 120 in response to a sensedcondition, as will be described below.

A number of exemplary stimulation parameters corresponding to a numberof different stimulation sites will now be described. However, it willbe recognized that the following descriptions are merely illustrative ofthe many different combinations of stimulation parameters andstimulation sites that may be used to treat obesity and/or type IIdiabetes.

In patients where the pituitary gland is stimulated to treat obesityand/or type II diabetes, the stimulation may be configured to modulatethe release of ACTH (adrenocorticotropic hormone) by the pituitarygland. ACTH acts on the cells of the adrenal glands, stimulating them toproduce glucocorticoids (e.g., cortisol). Cortisol promotes an increasein blood glucose. Hence, inhibiting the release of ACTH via inhibitorystimulation may lower the production of cortisol and/or otherglucocorticoids and thereby lower the blood glucose level. This loweringof the blood glucose level may be useful in treating type II diabetesand/or obesity. Moreover, it has been discovered that the overproductionof cortisol can lead to overeating and/or increased fat production inthe body. Hence, inhibition of the production of cortisol mayadditionally or alternatively be used to treat obesity and/or type IIdiabetes by preventing overeating and/or fat production.

In some alternative examples, excitatory stimulation may be applied tothe pituitary gland to increase the release of ACTH in order to treatobesity and/or type II diabetes. An increase in ACTH production may beconfigured to cause stress to the patient and thereby promote weightloss. Hence, either inhibitory and/or excitatory stimulation may be usedas may serve a particular application. In some embodiments, theparticular stimulation parameters used to control the stimulation of thepituitary gland may be determined based on patient feedback and/or on asensed indicator of obesity and/or type II diabetes, as describedpreviously.

In patients where the anxiety and/or pleasure centers within the brainare stimulated to treat obesity and/or type II diabetes, the stimulationmay be configured to prevent neural activity therein that usually occurswhen the patient eats. It has been discovered that when people withovereating problems eat, neural activity in the pleasure centerincreases and neural activity in the anxiety center decreases. Hence,food has an addictive effect for many such patients. Thus, thestimulation parameters may be configured to inhibit neural activitywithin the pleasure center and/or increase neural activity within theanxiety center when a patient eats so that the patient does not feel theaddictive effects. Without these addictive effects, the patient may beable to more easily form proper eating habits and thereby treat obesityand/or type II diabetes. In some embodiments, the particular stimulationparameters used to control the stimulation of the anxiety and/orpleasure centers may be determined based on patient feedback and/or on asensed indicator of obesity and/or type II diabetes.

In some examples, the stimulator 120 is configured to communicate withand/or receive power from one or more devices located external to thepatient. For example, an external battery charging system (EBCS) 201 maybe provided to generate power that is used to recharge the power source123 via any suitable communication link. Additional external devicesincluding, but not limited to, a manufacturing and diagnostic system(MDS) 203, a hand held programmer (HHP) 205, and/or a clinicianprogramming system (CPS) 207 may also be provided and configured toactivate, deactivate, program, and/or test the stimulator 120 via one ormore communication links. It will be recognized that the communicationlinks shown in FIG. 2 may each include any type of link used to transmitdata or energy, such as, but not limited to, an RF link, an infrared(IR) link, an optical link, a thermal link, or any other energy-couplinglink.

If multiple external devices are used in the treatment of a patient,there may be communication among those external devices, as well as withthe implanted stimulator 120. It will be recognized that any suitablecommunication link may be used among the various devices illustrated.

The external devices shown in FIG. 2 are merely illustrative of the manydifferent external devices that may be used in connection with thestimulator 120. Furthermore, it will be recognized that the functionsperformed by any two or more of the external devices shown in FIG. 2 maybe performed by a single external device.

Thus, one or more external devices may be provided to interact with thestimulator 120, and may be used to accomplish one or more of thefollowing functions:

Function 1: If necessary, transmit electrical power to the stimulator120 in order to power the stimulator 120 and/or recharge the powersource 123.

Function 2: Transmit data to the stimulator 120 in order to change thestimulation parameters used by the stimulator 120.

Function 3: Receive data indicating the state of the stimulator 120(e.g., battery level, drug level, stimulation parameters, etc.).

Additional or alternative functions may include adjusting thestimulation parameters based on information sensed by the stimulator 120or by other sensing devices.

The stimulator 120 of FIG. 2 is illustrative of many types ofstimulators that may be used in accordance with the systems and methodsdescribed herein. For example, the stimulator 120 may include animplantable pulse generator (IPG), a spinal cord stimulator (SCS), adeep brain stimulator, a drug pump, or any other type of implantabledevice configured to deliver a stimulus to a stimulation site within apatient. Exemplary IPGs suitable for use as described herein include,but are not limited to, those disclosed in U.S. Pat. Nos. 6,381,496,6,553,263; and 6,760,626. Exemplary spinal cord stimulators suitable foruse as described herein include, but are not limited to, those disclosedin U.S. Pat. Nos. 5,501,703; 6,487,446; and 6,516,227. Exemplary deepbrain stimulators suitable for use as described herein include, but arenot limited to, those disclosed in U.S. Pat. Nos. 5,938,688; 6,016,449;and 6,539,263. All of these listed patents are incorporated herein byreference in their respective entireties.

The stimulator 120 of FIG. 2 may alternatively include amicrostimulator. Various details associated with the manufacture,operation, and use of implantable microstimulators are disclosed in U.S.Pat. Nos. 5,193,539; 5,193,540; 5,312,439; 6,185,452; 6,164,284;6,208,894; and 6,051,017. All of these listed patents are incorporatedherein by reference in their respective entireties.

FIG. 3 illustrates an exemplary microstimulator 130 that may be used asthe stimulator 120 described herein. Other configurations of themicrostimulator 130 are possible, as shown in the above-referencedpatents and as described further below.

As shown in FIG. 3, the microstimulator 130 may include the power source123, the programmable memory 126, the electrical circuitry 125, and thepump 127 described in connection with FIG. 2. These components arehoused within a capsule 131. The capsule 131 may be a thin, elongatedcylinder or any other shape as best serves a particular application. Theshape of the capsule 131 may be determined by the structure of thedesired stimulation site and the method of implantation. In someexamples, the microstimulator 130 may include two or more leadlesselectrodes 132 disposed on the outer surface thereof.

The external surfaces of the microstimulator 130 may advantageously becomposed of biocompatible materials. For example, the capsule 131 may bemade of glass, ceramic, metal, or any other material that provides ahermetic package that will exclude water vapor but permit passage ofelectromagnetic fields used to transmit data and/or power. Theelectrodes 132 may be made of a noble or refractory metal or compound,such as platinum, iridium, tantalum, titanium, titanium nitride, niobiumor alloys of any of these, in order to avoid corrosion or electrolysiswhich could damage the surrounding tissues and the device.

The microstimulator 130 may also include one or more infusion outlets133 configured to dispense one or more drugs directly at a stimulationsite. Alternatively, one or more catheters may be coupled to theinfusion outlets 133 to deliver the drug therapy to a treatment sitesome distance from the body of the microstimulator 130.

FIGS. 4A-4C show alternative configurations of a microstimulator 130. Itwill be recognized that the alternative configurations shown in FIGS.4A-4C are merely illustrative of the many possible configurations of amicrostimulator 130. For example, FIG. 4A shows an example of amicrostimulator 130 with one or more leads 140 coupled thereto. As shownin FIG. 4A, each of the leads 140 may include one or more electrodes 141disposed thereon. The microstimulator 130 of FIG. 4A may additionally oralternatively include one or more leadless electrodes 132 disposed onthe outer surface thereof.

FIG. 4B illustrates an exemplary microstimulator 130 with a plurality ofelectrodes 132 disposed on an outer surface thereof. In some examples,any number of electrodes 132 may be disposed on the outer surface of themicrostimulator 130. In some alternative examples, as shown in FIG. 4C,the microstimulator 130 may be coupled to a lead 121 having a number ofelectrodes 122 disposed thereon. Each of the electrodes 132 and 122 maybe selectively configured to serve as an anode or as a cathode.

In some examples, the stimulator 120 of FIG. 2 may be configured tooperate independently. Alternatively, as shown in FIG. 5, the stimulator120 may be configured to operate in a coordinated manner with one ormore additional stimulators, other implanted devices, or other devicesexternal to the patient's body. FIG. 5 illustrates an exemplaryconfiguration wherein a first stimulator 120-1 implanted within thepatient 151 provides a stimulus to a first location, a second stimulator120-2 provides a stimulus to a second location, and a third stimulator120-3 provides a stimulus to a third location. In some examples, one ormore external devices 150 may be configured to control the operation ofeach of the implanted devices 120. In some embodiments, an implanteddevice, e.g., stimulator 120-1, may control, or operate under thecontrol of, another implanted device(s), e.g., stimulator 120-2 and/orstimulator 120-3. Control lines 152 have been drawn in FIG. 5 toillustrate that the external device 150 may communicate or provide powerto any of the implanted devices 120 and that each of the variousimplanted devices 120 may communicate with and, in some instances,control any of the other implanted devices.

As a further example of multiple stimulators 120 operating in acoordinated manner, the first and second stimulators 120-1 and 120-2 ofFIG. 5 may be configured to sense various indicators of the symptoms orcauses of obesity and/or type II diabetes and transmit the measuredinformation to the third stimulator 120-3. The third stimulator 120-3may then use the measured information to adjust its stimulationparameters and apply stimulation to a stimulation site accordingly. Thevarious implanted stimulators may, in any combination, sense indicatorsof obesity and/or type II diabetes, communicate or receive dataregarding such indicators, and adjust stimulation parametersaccordingly.

In order to determine the strength and/or duration of electricalstimulation and/or amount and/or type(s) of stimulating drug(s) requiredto effectively treat obesity and/or type II diabetes, various indicatorsof obesity and/or type II diabetes and/or a patient's response totreatment may be sensed or measured. To this end, the stimulator 120 maybe in communication with and/or include a sensing device configured tosense any of a number of indicators related to obesity and/or type IIdiabetes.

The indicators that may be sensed include, but are not limited to,activity of gastric pacemaker cells, one or more scents, masticationrates, pressure against the stomach wall, stomach distension, stomachstrain, naturally occurring electrical activity within the stomach(e.g., gastric slow waves), a rate of digestion of food within thestomach, and/or any other activity within the stomach. The indicatorsmay additionally or alternatively include gastrointestinal hormonesecretion levels, electrical activity of the brain (e.g., EEG),neurotransmitter levels, hormone levels, metabolic activity in thebrain, blood flow rate in the head, neck or other areas of the body,medication levels within the patient, patient input (e.g., when apatient has the urge to eat, the patient can push a button on a remotecontrol or other external unit to initiate the stimulation), temperatureof tissue in the stimulation target region, physical activity level(e.g., based on accelerometer recordings), brain hyperexcitability, oneor more indicators of collateral tissue stimulation, and/or detection ofmuscle tone (e.g., mechanical strain, pressure sensor, orelectromyography (EMG)). In some examples, the stimulator 140 may beconfigured to adjust the stimulation parameters in a closed loop mannerin response to one or more of these measurements.

By way of example, an exemplary method of treating obesity and/or typeII diabetes may be carried out according to the following sequence ofprocedures. The steps listed below may be modified, reordered, and/oradded to as best serve a particular application.

1. A stimulator 120 is implanted so that its electrodes 122 and/orinfusion outlet 129 are in communication with a stimulation site withina patient (e.g., in communication with the pituitary gland). As usedherein and in the appended claims, the term “in communication with”refers to the stimulator 120, stimulating electrodes 122, and/orinfusion outlet 129 being adjacent to, in the general vicinity of, inclose proximity to, directly next to, or directly on the stimulationsite.

2. One or more stimulation parameters are configured to treat obesityand/or type II diabetes.

3. The stimulator 120 is programmed with the one or more stimulationparameters configured to treat obesity and/or type II diabetes. Thestimulator 120 may then generate and apply at least one stimulus to thestimulation site in accordance with the stimulation parameters. Thestimulus may include electrical stimulation, drug stimulation, geneinfusion, chemical stimulation, thermal stimulation, electromagneticstimulation, mechanical stimulation, and/or any other suitablestimulation.

4. When the patient desires to invoke stimulation, the patient sends acommand to the stimulator 120 (e.g., via a remote control) such that thestimulator 120 delivers the prescribed stimulation to the stimulationsite. For example, the stimulation may be activated by the patient whena particular incident of obesity and/or type II diabetes is detected.The stimulator 120 may alternatively or additionally be configured toapply the stimulation to the stimulation site in accordance with one ormore pre-determined stimulation parameters and/or automatically applythe stimulation in response to sensed indicators of obesity and/or typeII diabetes.

5. To cease or decrease stimulation, the patient may turn the stimulator120 down or off (e.g., via a remote control).

6. Periodically, the power source 123 of the stimulator 120 isrecharged, if necessary, in accordance with Function 1 described above.

In other examples, the treatment administered by the stimulator 120,i.e., drug therapy and/or electrical stimulation, may be automatic andnot controlled or invoked by the patient. It will be recognized that theparticular stimulation methods and parameters may vary as best serves aparticular application.

FIG. 6 shows a flowchart of an exemplary method of treating obesityand/or type II diabetes, according to the principles that have beendescribed in more detail above. While FIG. 6 illustrates exemplary stepsaccording to one embodiment, other embodiments may omit, add to,reorder, and/or modify any of the steps shown in FIG. 6.

In step 161, a stimulator is provided. In step 162, one or morestimulation parameters are configured to treat obesity and/or type IIdiabetes. In step 163, the stimulator is programmed with the stimulatorparameters. In step 164, a stimulus configured to treat obesity and/ortype II diabetes in accordance with the stimulation parameters isgenerated. In step 165, the stimulus is applied with the stimulator tothe stimulation site.

The stimulator 120 may be implanted within a patient using any suitablesurgical procedure such as, but not limited to, small incision, openplacement, laparoscopy, or endoscopy. Exemplary methods of implanting amicrostimulator, for example, are described in U.S. Pat. Nos. 5,193,539;5,193,540; 5,312,439; 6,185,452; 6,164,284; 6,208,894; and 6,051,017.Exemplary methods of implanting an SCS, for example, are described inU.S. Pat. Nos. 5,501,703; 6,487,446; and 6,516,227. Exemplary methods ofimplanting a deep brain stimulator, for example, are described in U.S.Pat. Nos. 5,938,688; 6,016,449; and 6,539,263. All of these listedpatents are incorporated herein by reference in their respectiveentireties.

To illustrate, the stimulator 120 may be implanted beneath the scalp ofa patient to stimulate a stimulation site within the brain. For example,as shown in FIG. 7, the stimulator 120 may be implanted in asurgically-created shallow depression or opening in the skull 170. Thedepression may be made in the parietal bone 171, temporal bone 172,frontal bone 173, or any other bone within the skull 170 as may serve aparticular application. The stimulator 120 may conform to the profile ofsurrounding tissue(s) and/or bone(s), thereby minimizing the pressureapplied to the skin or scalp. Additionally or alternatively, thestimulator 120 may be implanted in a subdural space over any of thelobes of the brain, in a sinus cavity, or in an intracerebral ventricle.

In some embodiments, as shown in FIG. 7, a lead 121 and/or catheter 123run subcutaneously to an opening in the skull 170 and pass through theopening such that it is in communication with a stimulation site (e.g.,the pituitary gland) in the brain. Alternatively, the stimulator 120 isleadless and is configured to generate a stimulus that passes throughthe skull. In this manner, a stimulation site within the brain may bestimulated without having to physically invade the brain itself.

Alternatively, as shown in the cross-sectional view of FIG. 8, thestimulator 120 may be implanted within the lumen of a hole 180 createdin the skull 170 and configured to apply a stimulus at a stimulationsite within the brain (e.g., the pituitary gland). The hole 180 may be aburr hole, for example, and may be created with a surgical drill or anyother suitable device. The hole 180 extends at least partially into theskull 170. The stimulator 120 may be placed within the lumen of the hole180 and coupled to the walls of the hole 180 using an adhesive, suture,or any other fastening device. Once the stimulator 120 has beenimplanted, the hole 180 may be covered by an appropriately sized cap(not shown).

As shown in FIG. 8, a lead 121 may be coupled to the stimulator 120 withthe distal end of the lead 121 being routed to a particular location incommunication with a stimulation site within the brain (e.g., thepituitary gland). A distal portion of the lead 121 may include one ormore electrodes 122 configured to deliver an electrical stimulationcurrent to the stimulation site. A catheter (not shown) may additionallyor alternatively be coupled to the stimulator 120 and routed to thestimulation site so as to deliver one or more drugs at the stimulationsite.

In some examples wherein the stimulation site is the pituitary gland,the stimulator 120 may be implanted using a trans-sphenoidal approach.In other words, the stimulator 120 and/or lead 121 may be implantedthrough the sphenoid sinus just posterior to the nasal cavity. In thismanner, passage of the stimulator 120 and/or lead 121 through the tissueof the brain may be avoided.

It will be recognized that the implant locations of the stimulator 120described herein are merely illustrative and that the stimulator 120 mayadditionally or alternatively be implanted in any other suitablelocation within the body.

The preceding description has been presented only to illustrate anddescribe embodiments of the invention. It is not intended to beexhaustive or to limit the invention to any precise form disclosed. Manymodifications and variations are possible in light of the aboveteaching.

1. A method of treating a patient with at least one of obesity and typeII diabetes, comprising: providing a stimulator; configuring one or morestimulation parameters to treat at least one of obesity and type IIdiabetes; programming said stimulator with said one or more stimulationparameters; generating a stimulus configured to treat at least one ofsaid obesity and said type II diabetes with said stimulator inaccordance with said one or more stimulation parameters; and applyingsaid stimulus with said stimulator to a pituitary gland within saidpatient.
 2. The method of claim 1, further comprising determining saidstimulation parameters based on patient feedback.
 3. The method of claim1, wherein said stimulus is configured to modulate one or more hormonesproduced by said pituitary gland.
 4. The method of claim 3, wherein saidone or more hormones produced by said pituitary gland comprises anadrenocorticotropic hormone.
 5. The method of claim 4, wherein saidstimulus is configured to inhibit production of said adrenocorticotropichormone.
 6. The method of claim 4, wherein said stimulus is configuredto increase production of said adrenocorticotropic hormone.
 7. Themethod of claim 1, wherein said stimulator is coupled to one or moreelectrodes, and wherein said stimulus comprises a stimulation currentdelivered to said pituitary gland via said electrodes.
 8. The method ofclaim 1, wherein said stimulus comprises one or more drugs delivered tosaid pituitary gland.
 9. The method of claim 1, further comprisingsensing at least one indicator related to one or more effects of atleast one of said obesity and said type II diabetes and using said atleast one sensed indicator to adjust one or more of said stimulationparameters.
 10. The method of claim 1, further comprising using atrans-sphenoidal approach to implant said stimulator.
 11. A method oftreating strabismus, said method comprising: implanting a stimulator atleast partially within a patient; configuring one or more stimulationparameters to treat at least one of obesity and type II diabetes;programming said stimulator with said one or more stimulationparameters; generating a stimulation current configured to treat atleast one of said obesity and said type II diabetes with said stimulatorin accordance with said one or more stimulation parameters; and applyingsaid stimulation current with said implanted stimulator to a pituitarygland of said patient.
 12. The method of claim 11, wherein said stimulusis configured to modulate one or more hormones produced by saidpituitary gland.
 13. The method of claim 12, wherein said one or morehormones produced by said pituitary gland comprises anadrenocorticotropic hormone.
 14. The method of claim 11, furthercomprising sensing at least one indicator related to one or more effectsof at least one of said obesity and said type II diabetes and using saidat least one sensed indicator to adjust one or more of said stimulationparameters.
 15. The method of claim 11, wherein said step of implantingsaid stimulator comprises implanting said stimulator in accordance witha trans-sphenoidal approach.
 16. A system for treating a patient with atleast one of obesity and type II diabetes, said system comprising: astimulator configured to generate at least one stimulus in accordancewith one or more stimulation parameters adjusted to treat at least oneof obesity and type II diabetes; a programmable memory unit incommunication with said stimulator and programmed to store said one ormore stimulation parameters to define said stimulus such that saidstimulus is configured to treat said at least one of said obesity andsaid type II diabetes; and means, operably connected to said stimulator,for applying said stimulus to a pituitary gland of said patient.
 17. Thesystem of claim 16, wherein said stimulator is further configured todetermine said stimulation parameters based on patient feedback.
 18. Thesystem of claim 16, wherein said stimulus is configured to modulate oneor more hormones produced by said pituitary gland.
 19. The system ofclaim 18, wherein said one or more hormones produced by said pituitarygland comprises an adrenocorticotropic hormone.
 20. The system of claim16, wherein said means for applying said at least one stimulus comprisesone or more electrodes, and wherein said stimulus comprises astimulation current delivered via said electrodes.